1. Field of the Disclosure
The present invention relates to cellular propagation of hepatitis C virus (HCV) and the uses of HCV antigen produced in such cell systems.
2. Description of Related Art
Non-A, Non-B hepatitis (NANBH) is a transmissible disease (or family of diseases) that is believed to be virally induced, and is distinguishable from other forms of virus-associated liver disease, such as those caused by hepatitis A virus (HAV), hepatitis B virus (HBV), delta hepatitis virus (HDV), cytomegalovirus (CMV), or Epstein-Barr virus (EBV). Epidemiologic evidence suggests that there may be three types of NANBH: the water-borne epidemic type; the blood or needle associated type; and the sporadically occurring community acquired type. However, the number of causative agents is unknown.
Recently, however, a new viral species, hepatitis C virus (HCV) has been identified as the primary (if not only) cause of blood-associated NANBH (BB-NANBH). In 1987, scientists at Chiron Corporation (the assignee of the present application) identified the first nucleic acid definitively linked to blood-borne NANBH. See, e.g., EPO Pub. No. 318,216 (published May 31, 1989) and EPO Pub. No. 388,232 (published Sep. 19, 1990) or PCT Publ. No. WO 90/11089 (published Oct. 4, 1990).
Hepatitis C appears to be the major form of transfusion-associated hepatitis in a number of countries, including the United States and Japan. There is also evidence implicating HCV in induction of hepatocellular carcinoma. Thus, a need exists for an effective method for preventing and treating HCV infection: currently, there is none.
The demand for sensitive, specific methods for screening and identifying carriers of NANBV and NANBV-contaminated blood or blood products is significant. Post-transfusion hepatitis (PTH) occurs in approximately 10% of transfused patients, and NANBH accounts for up to 90% of these cases. The major problem in this disease is the frequent progression to chronic liver damage (25-55%).
Patient care, as well as the prevention of transmission of NANBH by blood and blood products or by close personal contact, requires reliable diagnostic and prognostic tools to detect nucleic acids, antigens, and antibodies related to NANBV. In addition, there is also a need for effective vaccines and immunotherapeutic therapeutic agents for the prevention and/or treatment of the disease.
Prior to the work performed through applicants' assignee, no etiologic agent for NANBH was identified. See, e.g., U.S. Pat. No. 4,952,494 relating to an assay to detect the presence of live NANBHV in vitro wherein mononuclear cells from bone marrow or peripheral blood are enriched with a growth factor and then incubated with a sample to be tested, and the number of colonies arising from incubation are counted and compared to a control; the presence of live hepatitis virus is related to the inhibition of colony growth; PCT Pub. No. WO 87/05930 (published Oct. 8, 1987), reporting triomas consisting of immortalized non-lymphocytic, non-malignant, human or non-human primate cell lines, including hepatocytes, central nervous system cells, and synovial cells, fused with mouse/human hybridomas, which are then infected with a purported etiologic agent of NANBH; and Hellings, et al., J. Virol. Method. 10:321-326 (1985), reporting that a preparation containing mono-nuclear leukocytes, which purportedly were mainly lymphocytes, isolated from a patient with NANBH, caused NANBH when infused into a susceptible chimpanzee.
More recent publications of interest include Jacob, et al., J. Infect. Dis. 161:1121-1127 (1990); and Jacob, et al., Abstract 490 of The 1990 International Symposium on Viral Hepatitis and Liver Disease, Apr. 4-8, 1990.